Aqueous flare elevation induced by transcorneal application of highly selective agonists for prostaglandin E2 receptor subtypes in pigmented rabbits: Effect of tetramethylpyrazine

• Published in: Prostaglandins & other lipid mediators Vol. 65; no. 4; pp. 189 - 198
• Main Authors: Kitagawa, Kiyotaka, Hayasaka, Seiji, Watanabe, Kazuhiko, Nagaki, Yasunori
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2001
• Subjects: Animals; Aqueous flare elevation; Aqueous Humor - drug effects; Aqueous Humor - metabolism; Area Under Curve; Blood-Aqueous Barrier - drug effects; Blood-Aqueous Barrier - physiology; Cornea - metabolism; Diffusion; Dinoprostone - administration & dosage; Dinoprostone - analogs & derivatives; Dinoprostone - pharmacokinetics; Dinoprostone - pharmacology; Drug Interactions; EP agonists; EP receptor; Male; Molecular Structure; Pigmentation; Pigmented rabbits; Protein Isoforms - metabolism; Pyrazines - administration & dosage; Pyrazines - pharmacokinetics; Pyrazines - pharmacology; Rabbits; Receptors, Prostaglandin E - agonists; Receptors, Prostaglandin E - metabolism; Tetramethylpyrazine; Time Factors; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacokinetics; Vasodilator Agents - pharmacology; EP agonists; Aqueous flare elevation; EP receptor; Pigmented rabbits; Tetramethylpyrazine
• ISSN: 1098-8823
• DOI: 10.1016/S0090-6980(01)00137-X

We examined the disruptive effect of highly selective agonists for prostaglandin E 2 receptor subtypes (EP 1, EP 2, EP 3 and EP 4) on the blood-aqueous barrier, and evaluated the inhibitory effect of tetramethylpyrazine, an active component of Ligusticum wallichii, on the elevation of aqueous flare induced by the EP agonists in pigmented rabbits. Highly selective EP agonists (ONO-DI-004, EP 1 agonist; ONO-AE1-259-01, EP 2 agonist; ONO-AE-248, EP 3 agonist; ONO-AE1-329, EP 4 agonist) at 12.5 to 250 μg/ml were transcorneally administered to the eyes of pigmented rabbits using a glass cylinder. Animals were pretreated intravenously with tetramethylpyrazine (10 or 30 mg/kg) 30 minutes before application of the EP 2 or the EP 4 agonist. Aqueous flare was measured using a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. After administration of ONO-AE1-259-01 or ONO-AE1-329, aqueous flare increased and then gradually decreased. ONO-DI-004 and ONO-AE-248 had almost no effect on aqueous flare elevation. The AUC of eyes in rabbits pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was significantly smaller than that of eyes in rabbits treated with ONO-AE1-259-01 alone. The AUC of eyes in rabbits pretreated with tetramethylpyrazine, 10 or 30 mg/kg i.v., was not significantly smaller than that of eyes in rabbits treated with ONO-AE1-329 only. The results indicated that EP 2 and EP 4 agonists induced aqueous flare elevation in pigmented rabbits, and that tetramethylpyrazine inhibited the aqueous flare elevation induced by the EP 2 agonist but did not suppress the elevation induced by the EP 4 agonist.